Our laboratory aims to improve male reproductive health by increasing our understanding of male germ cell RNA biology. In animals, reproductive failure has an extensive economic impact on our food supply and is a major challenge for modern meat and dairy production. In humans, the ability to control fertility is a fundamental right. Likewise, the capacity to have children if desired is an important aspect of an individual’s health and happiness. Yet, there are no commercially available male contraceptives and at least half of human infertility is a result of male factors, with at least a third of those due to unknown cause. Thus, improved reproductive fitness, safe contraceptives, and effective infertility treatments are essential components of overall animal and human health. However, these goals can only be achieved with a more detailed understanding of male germ cell biology. A cell’s RNA pool (the transcriptome) governs every aspect of its biology, from identity to function. The male germ cell expresses one of the most complex transcriptomes in the mammalian body and alterations of RNA processing have profound effects on germ cell development and fertility. Thus understanding what RNAs a germ cell makes, what those RNAs generate, and how they are regulated are key to understanding the basic biology of the male germ cell. Importantly, these findings may also have direct impacts on how we diagnose and treat infertility as well as develop safe, reversible male contraceptives.
Our current projects focus on two aspects of male germ cell RNA biology, using the mouse as a model:
1. The expression and function of novel RNAs that may encode new proteins
2. The regulation of nucleotide-level RNA modifications and how they impact protein production and fertility
Both projects combine methods from computational biology, molecular biology, biochemistry, genetics, and traditional reproductive physiology. Ultimately these studies will enhance our understanding of how RNA variants impact a cell’s proteins, cellular physiology, and male reproductive health.